Aging is associated with a decline in the activities of several enzymes which catalyze the synthesis of neurotransmitters in the brain and some of the behavioral impairments associated with aging may be the consequence of impaired function of these neural systems. In particular, the catecholaminergic systems appear to be affected during aging. Efforts will be made to examine the regulation of catecholamine synthesis, release and the postsynaptic changes associated with catecholamine release in young and aged rats in order to determine whether these systems are compromised with aging. The amount, activity and activation by cyclic AMP-dependent proteing kinase of tyrosine hydroxylase in different brain regions of young and aging rats will be determined both in vivo, following stress, and in vitro, following chemical or electrical stimulation of isolated brain tissue. The levels in different monoamine containing brain regions of tetrahydrobiopterin, the pterin cofactor for tyrosine and tryptophan hydroxylases, and of biopterin and dihydrobiopterin, will be examined in an analogous manner, both in vivo and in vitro. Release of catecholamines from isolated brain tissue following electrical or chemical stimulation and the effects of putative regulators of neurotransmitter release will be compared in young and aging rats. The effect of electrical and chemical stimulation of isolated brain slices and synaptosomes and the effects of cyclic AMP analogs, specific phosphodiesterase inhibitors and agonists known to activate adenylate cyclase in brain tissue on the phosphorylation of tyrosine hydroxylase, protein 1 and other soluble and membranous brain proteins will be examined in young and aging rats. Activation of protein kinases by these manipulations will also be assessed. The effects of stress on protein phosphorylation and protein kinases in brain will be evaluated in young and aged rats. These investigations should help to define the changes in catecholaminergic systems in brain during aging and the biochemical consequences of these alterations at the presynaptic and postsynaptic level in both stressed and unstressed animals. The studies should provide insight into the mechanisms which may account for the reduced ability of the aged animal to adapt to endogenous and environmental stresses.